The mechanism of differentiation, although important to our comprehension of the growth regulation of normal and neoplastic neuronal cells is, unfortunately, poorly understood. Nerve growth factor (NGF) is a well characterized polypeptide hormone involved in regulating the growth and differentiation of the nervous systm. NGF can also promote morphological differentiation of neuroblastoma and pheochromocytoma in vitro. The objective of this proposal is to: 1) investigate tumors of the autonomic nervous system, such as neuroblastoma, pheochromocytoma, and neurofibromatosis for defects in their binding properties and response to NGF; and 2) investigate the mechanism of morphological differentiation in pheochromocytoma by selection of appropriate mutants. The aim is to define the entire pathway and to identify and isolate cellular components regulating axon formation and biochemical specialization.